Discovery of MCJ protein's role in converting brown fat to heat could combat obesity

Good news!

"... have discovered one of the ways in which the body "burns" brown fat and converts it into heat. This mechanism protects against obesity and related metabolic diseases.

The mechanism now identified is controlled by the protein called MCJ, present in mitochondria ...

have discovered that, when the MCJ protein is removed from obese mice, these animals produce more heat and lose weight. The researchers have also managed to reduce the weight of obese mice just by having them transplanted with fat without that protein. ...

For a long time it was thought that brown fat used a single mechanism to generate heat, but today we know that this is not the case. There are several mechanisms involved. The research ... has discovered one of them, controlled by a mitochondrial protein called MCJ. ...

The researchers also observed that "animals without MCJ in brown fat are protected against health problems caused by obesity, such as diabetes or increased blood lipids," ... Therefore, they believe that the MCJ protein could be a new therapeutic target to correct diseases associated with obesity."

From the abstract:

"Obesity poses a global health challenge, demanding a deeper understanding of adipose tissue (AT) and its mitochondria.

This study describes the role of the mitochondrial protein Methylation-controlled J protein (MCJ/DnaJC15) in orchestrating brown adipose tissue (BAT) thermogenesis. Here we show how MCJ expression decreases during obesity, as evident in human and mouse adipose tissue samples. MCJKO mice, even without UCP1, a fundamental thermogenic protein, exhibit elevated BAT thermogenesis.

Electron microscopy unveils changes in mitochondrial morphology resembling BAT activation. Proteomic analysis confirms these findings and suggests involvement of the eIF2α mediated stress response. The pivotal role of eIF2α is scrutinized by in vivo CRISPR deletion of eIF2α in MCJKO mice, abrogating thermogenesis. These findings uncover the importance of MCJ as a regulator of BAT thermogenesis, presenting it as a promising target for obesity therapy."

Discovery of MCJ protein's role in converting brown fat to heat could combat obesity

Nature Communications. CNIO research identifies a key protein for ‘burning’ fat (original news release)

Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis (open access)

Fig. 1: The absence of MCJ protects against obesity increasing interscapular temperature while not affecting the metabolism on chow diet.

Fig. 2: BAT-specific MCJ deficiency increases BAT temperature protecting against obesity.

Some of the researchers involved in this study. From the left: Beatriz Cicuéndez, Guadalupe Sabio, Marta León and Cintia Folgueira. / Laura M. Lombardía. CNIO.